“Hotspot” is one of those extremely versatile words, similar to “model” and “buffer”, which can mean a variety of things depending on context. According to Merriam-Webster, a hotspot is “a place of more than usual interest, activity, or popularity”. This is the most general definition of the concept I could find in a quick search, and the one I find closest in spirit to the way hotspots are perceived in a structural biology context. What this blog post is definitely not about are hotspots as “areas of political, military, or civil unrest” (my experience with them has so far been mostly peaceful), or anything to do with geology, WiFi connections, or forest fires.
However, even within the context of structural biology and structure-based drug design, the word “hotspot” has multiple meanings. In this blog post, I will try to summarise the main ones I have come across, the (sometimes subtle) differences between them, and provide a few useful papers to serve as an entry point for interested readers. Continue reading →